Mechanistically, primary resistance often stems from tumor–immune escape at multiple levels of the cancer–immunity cycle: deficient antigen presentation (e.g., downregulation of HLA-I or loss of β2-microglobulin), oncogenic pathway activation (e.g., STK11, KEAP1, EGFR/ALK aberrations) and an immunosuppressive microenvironment with low T-cell infiltration or high myeloid-derived suppressor cell (MDSC) load [91]. Here, ALK is linked to neoplasm.